Structural insights into selective recognition of ATP-mimicking inhibitors by the atypical kinase HASPIN
Sang Won Cheon, Yun A Yum, Donghwan Ku, Sung Chul Jang, Vikas R Aswar, Dnyandev B Jarhad, Yoonyoung Heo, Hyoun Sook Kim, Sang Kook Lee, Lak-Shin Jeong, Byung Woo Han · 2026
Read Structural insights into selective recognition of ATP-mimicking inhibitors by the atypical kinase HASPIN by Sang Won Cheon, Yun A Yum, Donghwan Ku, Sung Chul Jang, Vikas R Aswar, Dnyandev B Jarhad, Yoonyoung Heo, Hyoun Sook Kim, Sang Kook Lee, Lak-Shin Jeong, Byung Woo Han (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/PMC13527128.txt.
Description
Sang Won Cheon and colleagues report, in a 2026 structural study, how the atypical kinase HASPIN selectively recognizes two inhibitors that mimic ATP, the cell's energy currency. Kinase drug design struggles for selectivity because the ATP pocket looks similar across hundreds of kinases. HASPIN, a kinase active in germ cells, offered a test case for ATP-like scaffolds.
Crystal structures of the enzyme bound to each inhibitor, solved at high resolution, showed ATP-like poses inside the catalytic pocket. The protein's internal spines were preorganized by dense hydrophobic packing, holding a key helix in place without any nucleotide present. Despite similar poses, one compound bound about ten times more tightly and showed roughly tenfold stronger enzyme inhibition and hundredfold stronger cell-killing selectivity. The pocket's distinctive architecture explains the discrimination.
Catalog record
| CREATOR | Sang Won Cheon, Yun A Yum, Donghwan Ku, Sung Chul Jang, Vikas R Aswar, Dnyandev B Jarhad, Yoonyoung Heo, Hyoun Sook Kim, Sang Kook Lee, Lak-Shin Jeong, Byung Woo Han |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 46133 |
| LICENSE | https://creativecommons.org/licenses/by/4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |